Prospective Comparative Study of Topical Tacrolimus and Sirolimus for the Treatment of Pigmentary Keratitis in Pug Dogs

Abstract

Pigmentary keratitis (PK) is a prevalent ocular surface disease in Pug dogs, yet comparative evidence on topical immunosuppressants remains limited. This prospective comparative clinical study evaluated the efficacy and safety of two agents with distinct mechanisms—tacrolimus, a calcineurin inhibitor, and sirolimus, an mTOR inhibitor—for the treatment of PK. Thirty-two Pugs (63 eyes) were randomly assigned to receive either 0.03% tacrolimus or 0.03% sirolimus three times daily for six months. Tear film quantity and quality were assessed using the Schirmer tear test, tear break-up time, and Ferning patterns, alongside serial clinical scoring of corneal pigmentation and ocular surface signs. Both treatments improved tear-film parameters, although only tacrolimus produced statistically significant increases in tear production and more frequent formation of a pigment-free “clear line,” indicating enhanced pigment regression. Pigment lightening and transparency recovery improved similarly in both groups. Adverse events—including blepharospasm, diffuse corneal oedema, and complicated ulcers—occurred more frequently in the sirolimus group, suggesting a comparatively less favorable short-term safety profile. Overall, both tacrolimus and sirolimus demonstrated therapeutic benefit in PK, although tacrolimus showed superior quantitative efficacy and better tolerability. Further long-term studies are warranted to clarify safety considerations and to optimize immunomodulatory strategies for this breed-specific condition. These findings suggest tacrolimus may be considered a first-line immunomodulatory therapy for PK in Pug dogs.